Evaluation of hepatic masses by multidetector CTA

By Elliot K. Fishman, MD

Image Gallery

Dr. Fishman
is a Professor of Radiology and Oncology and the Director of
Diagnostic Radiology and Body CT at Johns Hopkins Medical
Institutions, Baltimore, MD.

In some ways, computed tomography (CT) of the liver has not
changed in 25 years. The goals of imaging remain the detection of
disease, definition of the extent of disease, determination of the
etiology of hepatic masses, and assistance with patient management
decisions. What has changed markedly is scanner technology and
contrast delivery and, therefore, our ability to accomplish these
goals.

Improvements in scanner technology, particularly multidetector
technology, have played a critical role in optimizing lesion
detection. Advances in scanning techniques and protocols, including
the use of double- and triple-phase scans, have also been important
in improving sensitivity for disease detection, and in many cases,
specificity. Better image analysis and interpretation, particularly
the replacement of axial image analysis with real-time
three-dimensional (3D) visualization, will continue to grow in
importance over the next several years.

This article will review the basic principles of hepatic
imaging, protocol design, clinical applications, and image analysis
and interpretation, including the role of two-dimensional (2D) and
3D visualization.

Protocols

In addition to improving lesion detection, 16-slice scanners
have simplified the timing of contrast injection and data
acquisition. Rather than using multiple bolus injections of
contrast material, or a combination of contrast bolus and slow
infusion, at our institution, we are now able to inject a single
bolus of contrast material. For diagnostic liver examinations, we
use oral water as a negative contrast agent. We also typically
inject 100 to 120 mL of Omnipaque 350 (GE Healthcare, Princeton,
NJ) or Visipaque 320 (GE Healthcare) intravenously at a rate of 3
to 4 mL/sec.

We frequently provide volume displays to referring physicians,
particularly surgical oncologists, for use in preoperative
planning. Therefore, although the specific scanning protocol will
vary by scanner, we routinely select imaging settings that optimize
lesion detection, including the use of smaller detectors (0.75 mm),
a narrow slice thickness (0.75 mm), and close interscan spacing
(0.5 mm) (Table 1).

We generally evaluate liver lesions using both arterial- and
venous-phase imaging, although single-phase imaging may be
sufficient in some cases, particularly for follow-up studies. Since
the introduction of the 16-slice scanner, some authors have
examined the potential advantages of doing not only classical
arterial-phase imaging at 25 seconds, but also early-phase arterial
imaging at approximately 15 seconds. Although some studies have
reported reasonably good results with this approach, most have
suggested that scanning at 15 seconds is too early to improve
detection of hepatic lesions.
1,2

We generally initiate arterial-phase imaging at about 25 seconds
and venous-phase imaging at 60 seconds. We reserve late-phase
imaging (3 to 4 minutes after injection) for cases in which we may
be uncertain of a specific diagnosis or for selected applications
in which the contrast density of lesions continues to increase over
time. The evaluation of suspected cholangiocarcinoma is one such
example.

Vascular mapping

Hepatic lesions have long been described as hypervascular or
hypovascular, but little attention has been paid to specific
vascular anatomy, such as feeding vessels, draining vessels, and
the degree of neovascularity. This information can now be drawn
from CT data sets and can markedly improve patient management.

Arterial mapping is of critical importance in preoperative
planning. Variations in hepatic anatomy-hepatic and splenic
arteries that arise directly off the aorta, for example (Figure
1)-are easily defined on an angiographic study. Similarly, venous
mapping provides information that is essential to preparing for
complicated surgical procedures (Figure 2).

With the aid of volumetric vascular maps, surgeons are better
able to select patients for surgery, plan more carefully for liver
transplantation, and perform more aggressive hepatic resections,
among other procedures. Vascular mapping is also an important
postoperative tool for the evaluation of surgical
complications.

Benign hepatic tumors

Benign hepatic tumors are among the most common lesions examined
by CT. This category includes hepatic cysts, hemangiomas, focal
nodular hyperplasia (FNH), and hepatic adenomas. Many of these
lesions do not require intervention. It is important, therefore,
that imaging differentiates benign from malignant lesions and
provides accurate patient management information to referring
physicians.

Hepatic cysts occur in 10% of patients and are the most common
type of benign hepatic lesion. They range in size from a few
millimeters to 15 to 20 cm (Figure 3). Hepatic cysts are generally
very well defined, although small cysts may be difficult to detect
on thick-section axial imaging, as a result of partial-volume
averaging.
3

Typically, hepatic cysts do not displace blood vessels, and when
they do, the displacement is very smooth. Most patients with a
hepatic cyst are asymptomatic; however, if the cyst is large
enough, it can compress the inferior vena cava and cause
lower-extremity edema. In addition, we have seen very large cysts
cause ascites due to venous obstruction that necessitate hepatic
resection.

Hepatic hemangiomas are also common, particularly in women. They
typically occur in the right lobe of the liver, usually in the
periphery. Often detected incidentally (Figure 4), they are
characterized by peripheral enhancement and central filling-in over
time.

In some cases, it may be difficult to differentiate a small
hemangioma from a metastatic vascular tumor. A volume display,
rather than single axial slices, may be helpful. A
maximum-intensity projection (MIP), for example, will make the
diagnosis of hepatic hemangioma more certain by demonstrating very
bright peripheral puddling. By comparison, metastatic vascular
tumors or primary hepatomas typically do not have a peripheral
encasement pattern but instead have a more diffuse and irregular
enhancement pattern.
4,5

Another characteristic to consider in distinguishing hemangioma
from vascular metastasis is the appearance of the vessels supplying
the lesion. The vessels supplying a hemangioma are sometimes
prominent, but they typically are smooth and normal in appearance.
A malignant tumor generally is characterized by irregular,
corkscrewing vessels or neovascularity.

With today's fast CT scanners, FNH is observed more often now
than it was in the past. These lesions are very vascular and may
become isodense within approximately 30 seconds (Figure 5). In the
past, when imaging primarily took place during the portal or
late-venous phase, the lesion would already have become isodense at
the time of image acquisition. Now, with arterial- and dual-phase
imaging, FNH lesions are observed more often.
6

Most patients with FNH are women, and <20% have symptoms.
These lesions have no malignant potential. In fact, many consider
FNH to be a response of the liver parenchyma to a pre-existing
vascular malformation. It is very common to see an arteriovenous
malformation or hemangioma in patients with FNH.
7

Often with dual-phase imaging, a central scar can be observed in
the arterial phase. A scar is not diagnostic for FNH (it is also
observed with other lesions such as giant hemangiomas, hepatomas,
and cholangiocarcinomas), but it is a classic finding, particularly
when it fills in on late-phase imaging. Volumetric vascular maps,
by showing the anomalous feeding artery and hepatic venous drainage
that are also characteristic of FNH, enable the surgeon to
preoperatively plan removal of the lesion.
8

Hepatic adenomas, although benign lesions, have malignant
potential and can develop into hepatomas. Hepatic adenomas range in
size from 1 to 15 cm. Some 70% to 80% are solitary, although
multiple lesions are common in patients with glycogen storage
disease or liver adenomatosis. In addition, these lesions can
spontaneously bleed, particularly large or multiple lesions.
7

Hepatic adenoma can be differentiated from FNH by differences in
attenuation and contrast enhancement in the arterial phase.
9
Typically, FNH enhances to a greater degree than does an adenoma.
In one study, the average attenuation value in the arterial phase
was 118 ± 18 HU for FNH, as compared with 80 ± 10 HU for hepatic
adenoma.
7
This observation does not always hold true in clinical practice,
however.

Malignant hepatic tumors

The optimal contrast-enhancement phase, or phases, for the
detection of a hepatoma is a matter of debate. It remains an
important question in the management of patients with hepatitis B
and C, who undergo frequent screening scans.

Hepatoma lesions become isodense very quickly. In the past, with
single-slice scanners, arterial-phase imaging was preferred. Today,
the ability to acquire images during multiple phases in a short
period of time affords us much more flexibility. Research has not,
however, provided clear guidance as to the best approach to
screening for hepatoma.

Peterson et al
10
studied triphasic imaging in 430 patients with hepatitis B and C.
They found that hepatocellular carcinoma was detected most often
during the arterial phase.

Kim et al
11
examined the effectiveness of 4-phase imaging, including an early
arterial phase (15 seconds after contrast injection). This
additional early phase was not found to substantially improve
lesion detection, however.

Lim et al
12
evaluated triphasic imaging and found that a combination of
late-arterial and portal-venous phases maximized the efficiency of
lesion detection.

In some cases, unenhanced scans are helpful as well. This is
especially true in cases in which the mass may be a regenerating
nodule, which may be hyperdense on noncontrast CT scans.

As indicated earlier, at our institution, we generally use a
combination of arterial- and venous-phase imaging, initiating
arterial-phase acquisitions at about 25 seconds and venous-phase
acquisitions at 60 seconds.

In the examination of hepatic masses, a volume display can yield
far more information than axial slices alone. A MIP image, for
example, can define the borders of the lesion and demonstrate the
feeding vessels and abnormal corkscrewing of the vasculature
(Figure 6). The ability to depict neovascularity improves the
detection of very small lesions and adds substantial value to the
screening of patients with hepatitis B and C. A volume display can
determine resectability of a lesion by showing whether it has
directly invaded the portal vein, the inferior vena cava, or even
the heart. It can also show arteriovenous shunting and guide
embolization therapy.

Not every patient who develops hepatoma has cirrhosis or another
underlying liver disease. In fact, some have no risk factors for
hepatoma. Such patients tend to have larger lesions. In a study by
Brancatelli et al,
13
39 patients with hepatoma in the absence of cirrhosis underwent CT
scanning. The average tumor size was 12.4 cm. These investigators
also noted that in 4 patients, the lesions contained fat and
suggested that a finding of fat in a hypervascular hepatic lesion
should raise suspicion for hepatoma.
13
Such a finding is also consistent with benign angiolipoma,
however.

It is sometimes necessary to differentiate hepatoma from
regenerative nodules. As shown in Figure 7, a regenerative nodule
will often enlarge on venous-phase imaging. Generally, a hepatoma
lesion either remains the same size in arterial- and venous-phase
imaging, or becomes smaller on the later-phase studies.

Metastatic disease

Metastatic liver lesions may be hypovascular or hypervascular.
In the past, CT has been more successful in detecting and
characterizing hypovascular lesions-for example, metastases from
colorectal cancer. Valls et al
14
used helical CT in the preoperative evaluation of 119 patients with
colorectal metastases, reporting that CT successfully identified
candidates for hepatic resection 94% of the time.

Today, with CT angiography and multiphase imaging, it is
possible to accurately detect hypervascular lesions as well. These
include metastases from carcinoid tumors, islet cell tumors, and
renal cell carcinomas. Figure 8 shows metastases to the liver from
a carcinoid tumor. The lesions, which are <1 cm in size, are
revealed on the 3D volume-rendered image by their feeding
vascularity.

With larger lesions, 3D vascular mapping may not improve lesion
detection, but it can display the extent of the lesion and depict
both the feeding arterial vessels and the rapid venous drainage
into the inferior vena cava. It may also de-monstrate occlusion of
vessels adjacent to the liver.
15,16

Conclusion

The use of proper scan protocols, the optimization of contrast
delivery, and the selection of appropriate phase of image
acquisitions are the keys to high-quality liver imaging.
Sixteen-slice CT scanners offer significant advantages over
earlier-generation technology and enable postprocessing to become a
routine procedure. This technology also enhances many of the
signature characteristics of tumors, enabling not only detection,
but also specific identification. This is especially valuable for
confidently determining whether small lesions are benign or
malignant.

Discussion

W. DENNIS FOLEY, MD:
One of the issues we have at our institution is imaging of patients
for liver transplant evaluation in whom we find a small, 1-cm,
hypervascular region. The question is: Is it a smaller
hepatocellular carcinoma or not? You just brought out something
that suggests you may have a means to make the distinction between
a benign nodule and a malignant nodule. Could you expand on that
and give us your practical approach at Hopkins?

ELLIOT K. FISHMAN, MD:
Dennis, I know you've written a lot on this subject. The smaller
lesions have always been a challenge for us, particularly in a
high-risk patient. Obviously, you can look at carcinoembryonic
antigen (CEA) and things like that. But one thing we have found is
that looking very carefully at the vascular pathway of the lesion
may help you. If you see neovascularity, it is a home-run
diagnosis.

One of the important conclusions from this series of lectures is
that axial CT is only the first step. There is so much information
in CT data sets that, for years, we were not able to draw out. Now
we are able to look at that information routinely. The liver is a
good example. We have never really spoken about vascularity. We
speak about hypervascular and hypovascular lesions, but there has
been little discussion of feeding vessels or draining vessels.
Based the angiographic literature for the last 30 years, it is no
great surprise that there is tremendous information there. What we
can do now with CT angiography is to really take advantage of
classic CT and classic angiography and improve what we can do by
putting those two together.

Once we can show the surgeons neovascularity, it will drive more
biopsies. So we can be very focused as to the biopsy site and which
patients we should biopsy. Again, these patients are often at a
high risk for biopsies because of their bleeding problems and with
regard to surgical planning, in terms of the likelihood of the
lesion being a hepatoma. So it is changing how we practice, and our
liver surgeons really rely on that.

U. JOSEPH SCHOEPF, MD
: The surveillance and screening of patients with cirrhosis or
hepatocellular carcinoma has always been challenging. It has been
argued that, especially in patients with cirrhosis, the tissue of
the liver is so brittle and the vascular resistance is so high that
we have a hard time getting in the amount of contrast that is
needed to detect those lesions, regardless how fast you scan or how
thin the slices are in those patients. Do you believe there is a
way around this with particular use of contrast agents?

FISHMAN
: I have no doubt that a patient with cirrhosis is a challenge, and
always has been a challenge with CT, MR, or ultrasound. People have
looked at different contrast agents, particularly in the research
environment, to see what can be done differently. There are a few
things that are being worked on. But, in my experience over the
last 2 years with 16-slice CT, we have a lot of information we can
gain that we were just not looking at before. One of the things
that has not yet been examined in a very systematic fashion is what
we can do with CT/pathologic direct correlation. It would be
particularly useful in patients who undergo transplants where you
can really slice the liver very carefully. If you look at the
literature in the past, even through 4-slice CT, the results are
very poor. Comparisons of CTfindings to a surgical specimen have
not provided the greatest results. But I agree with you, it is a
challenge, but I think it is a challenge we are better able to cope
with now than we have been before. Although, we do not have the
statistics yet; 16slice CT has been around for roughly a year and a
half, and there are no relevant large series published for it on
many applications. It takes a few years to have that data published
since the studies have to be done, the data collected, then an
article written and published. But it needs to be done because we
need true data.

BRIAN R. HERTS, MD:
Elliot, we also do a lot of liver transplant evaluations and we are
still doing a fair number of ultrasound exams to look at the
vasculature. At your institution, is CT angiography eliminating the
ultrasound exams that are often performed? Are you just performing
a CT?

FISHMAN
: I think it is variable. One of the things that changes from
institution to institution is how aggressive you are in doing any
particular technique. If you are really dedicated to working hard
at a technique, you are providing really good clinical service, you
have a lot of expertise, and you deal with physicians directly,
there is a greater tendency that that technique will be the most
valuable one.

I don't want to imply that we are not doing a lot of ultrasound
at Hopkins. But we spend a lot of effort on CT and the surgeons are
very comfortable with it, so that has been a great tradition for
us. We do tend to do a lot of CT. Also, some of the surgeons in the
transplant service have trained at other institutions where they
also relied on CT, so they have carried that over. It has been a
combination of what we do and what the surgeons are used to and
what they expect to get.

HERTS
: These are the recipients. We still do CT for lesion detection,
but they are still ordering ultrasound for everyone for portal vein
thrombosis or for direction and degree of portal hypertension. I'm
wondering if it would be a useful effort to start giving them
angiographic images and see if we can we stop using the ultrasounds
now.

FISHMAN
: There is no doubt in terms of any single study, the more
information you give from a single study, the better. You imaged
the renal donors with CTA and you replaced ultrasound, IVP, regular
CT, and everything else. If you can take a study and can provide a
lot of information to the referring physician, it may eliminate the
need for other studies, regardless of the application. It is
certainly something to look at.

LAWLER
: I think I am a healthy skeptic. But I have a question about when
you look at dual-phase imaging of any organ, or both kidney and
liver, with multidetector CTs. I wonder sometimes, with the quality
of the images, how much you really need dual-phase imaging-whether
it is just for vascular imaging, not lesion imaging. On the
portal-venous phase, in my experience, the arterial anatomy is
superb, and, indeed, with the kidney I also find sometimes it is
quite superb on the venous phase. Do you really just want to know
branch patterns and where they are? There's no doubt that it is a
prettier image if you just have arterial enhancement. But does it
add an awful lot more information? Then you could actually get away
with a short single-phase acquisition.

FISHMAN
: I think it would depend on the organ. One of the things we find
in the published literature, for example in a patient with
cirrhosis, is that often those small hepatomas will be seen only on
arterial-phase imaging. In terms of vascular imaging, it depends on
the situation. In our department, Satomi Kawamoto is looking at
that situation in terms of renal donors. We have traditionally done
two phases, and the question was, can one phase do it? What we are
seeing statistically is that this is the case.

LAWLER
: These are liver donors, obviously, rather than people with
lesions and so forth.

FISHMAN
: If you are looking at a liver donor per se, it depends on the
type of detail. If you do two acquisitions, you really can optimize
the small arterial vessels on arterial-phase imaging. If you want
good venous anatomy, it is at 60 seconds for venous-phase imaging.
The key is protocol design.

HERTS
: I have a hard time displaying some of the smaller vessels using
the venous phase, and I really have to work to bring them out. They
are probably there, but it is much harder to manipulate the
rendering to show them. Whereas using the vascular phase, with many
of the preset protocols on the workstations, the vasculature pops
up without much effort. It takes less than 10 seconds to find all
the arteries, and it is much faster than reading a CT axial image
by scrolling back and forth.

GEOFFREY D. RUBIN, MD
: You also have to think about what the referring clinicians are
looking for. Sometimes having that isolated arterial map is really
what they insist upon. If you give them an admixture of arteries
and veins, then you have to point it out.

LAWLER
: That's another good point. I think one of the shortcomings of a
lot of the segmentation tools has been that, once you get the
venous phase, you are not able to segment out veins, either portal
or hepatic. Having a separate hepatic artery phase makes it very
difficult. On the venous-phase imaging, we still have a lot of
arterial opacification. So, if someone asks me to just show the
hepatic veins, we can do it, especially if you have an interactive
movie. You want to give them a select image where it has just been
segmented, but I think some of the software has been a little bit
behind on that.

RUBIN
: Well, particularly if you are getting a biphasic acquisition, the
logical way to do the segmentation is with a subtracted image. I
think what is lacking in sophistication with all of our CT
postprocessing is good registration of nonrigid transformations,
which is what occurs when you get a different breath-hold. Moving
forward with postprocessing-that is going to be a big area for
improvement, and it will open up a lot of avenues for useful
visualization.